1. Field of the Invention
This invention relates to the use of .alpha..sub.1 -adrenoreceptor antagonists, or pharmaceutically acceptable acid addition acid addition salts thereof, for treating or preventing the formation of cancers. More particularly, it relates to a method for preventing the formation of, or reducing, such cancers in mammals by administering to said mammals an effective amount of an .alpha..sub.1 - adrenoreceptor antagonist or pharmaceutically acceptable acid addition salt thereof.
2. General Background
Cancer incidence is now at a level whereby it is predicted that it will be the primary cause of death in the United States by the year 2000. Although some advances have been made in the treatment of cancers individual mortality, in those over the age of 65, has not changed. Prostate cancer, predominantly in males over sixty-five years of age, has become an ever increasing problem in the developed countries of the world where men are living to older ages. Among males it is now the second greatest cause of cancer deaths. In the United States it was the cause of about 3% of all deaths (about 35000) in 1993. It has been predicted that the number of prostate cancer patients will increase dramatically over the next decade due to demographic changes in the population.
Early studies of phenoxybenzamine (a nonselective .alpha..sub.1 and .alpha..sub.2 adrenoreceptor antagonist) and prazosin (a selective .alpha..sub.1 adrenoreceptor antagonist) were effective in the treatment of smooth muscle effects of BPH with the selective .alpha..sub.1 agent producing fewer and more tolerable side effects than the nonselective phenoxybenzamine.
Kenny, B. et al. (.alpha..sub.1 -Adrenoreceptor Antagonists As Treatments For Benign Prostatic Hyperplasia, Exp. Opin. Invest. Drugs, (1995), 4(10), 915-23), incorporated herein in its entirety by reference) have discussed the use of a number of .alpha..sub.1 -adrenoreceptor antagonists, such as terazosin, doxazosin, indoramin and tamsulosin for the treatment of symptoms of BPH. However, they did not suggest that .alpha..sub.1 -adrenoreceptor antagonists could be used to prevent the formation of cancers or, if formed, treatment thereof to decrease the tumors.
Kaplan, S. A. et al, (Urology, 46(4), 1995, 512-17), Kirby, R. S. (Urology, 46(2), 1995, 182-6) and Fawzy, A. et al. (The Journal of Urology, 154, 105-9 (1995)) have discussed the effect of doxazosin on the blood pressure of normotensive men who are being treated with doxazosin for mediation of the dynamic component of smooth muscle prostate outflow obstruction.
Doxazosin, 4-amino-2-4-(1-4-benzodioxan-2-carbonyl)piperazin-1-yl!-6,7-dimethoxyquin azoline and its pharmaceutically acceptable acid addition acid addition salts, are described in U.S. Pat. No. 4,188,390 together with their use as regulators of the cardiovascular system, especially in the treatment of hypertension.
U.S. Pat. No. 4,758,569 claims the use of doxazosin in retarding development of atherosclerosis in a mammal. The use of trimazosin or a pharmaceutically acceptable acid salt thereof, for retarding atherosclerosis is described and claimed in U.S. Pat. No. 4,582,832.
U.S. Pat. Nos. 4,868,216 and 4,987,152 claim the use of tamsulosin and its hydrochloride for producing .alpha..sub.1 -adrenoreceptor antagonistic action, or treating urinary tract dysfunction, respectively, in a host.
.alpha..sub.1 -Adrenoreceptor antagonists such as 2,4,6,7-tetrasubstituted quinazolines are disclosed in U.S. Pat. Nos. 3,511,836, 4,001,237 and 4,188,390 for use as hypertensive agents. U.S. Pat. No. 4,112,097 also claims the use of terazosin, and its tetrahydropyran-2-carbonyl homologue, for treatment of hypertension in mammals.
Despite the many patents and studies, such as those above, relating to the use of .alpha..sub.1 -adrenoreceptor antagonists in the treatment of hypertension, atherosclerosis, urinary tract dysfunction and smooth muscle tone in BPH there have been no report of any teaching or suggestion that .alpha..sub.1 -adrenoreceptor antagonists, metabolites or their pharmaceutically acceptable acid addition acid addition salts could be used to prevent the formation of, or reduce cancerous tumors in a mammal.